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| Status |
Public on Nov 01, 2015 |
| Title |
The Prion Protein (PrP) is involved in translation via RNA granule-like mRNPs, a connection which is impaired during neurodegenerative diseases |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome variation profiling by high throughput sequencing
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| Summary |
Cytoplasmic RNA granules have emerged as important elements of posttranscriptional and translational regulation. Stress, germinal and neuronal granules contain RNA-binding proteins capable of self-assembly due to prion-like domains. Hyperassembly mediated by these prion-like domains causes several neurodegenerative diseases. Here, we report a subset of the mammalian prion protein (PrP), also prone to self-assembly, propagation and to cause devastating diseases, is a component of naturally occurring messenger ribonucleoproteins (mRNPs) in adult mouse brains. Biomolecules co-purified with PrP revealed a multitude of diverse RNA granule associated proteins and mRNAs encoding members of the translation machinery, indicating a role in a specialized translation process. Importantly, PrP mutations linked to Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI) severely impaired recovery of mRNPs from preclinical mice, possibly representing a very early pathological process. Thus, mutant PrP may cause dysfunction in RNA regulation, thereby joining the constantly expanding ranks of disease associated RNP granule proteins.
The file Enrichment_analysis.xlsx contains mRNAs (FDR < 0.01) co-purified with PrP in both WT sample pools as identified by DESeq2 and the respective gene counts and log2 fold changes for CJD and FFI PrP:IP sample pools.
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| Overall design |
RIP-Seq analysis of mRNAs co-purified with PrP from murine brain cytoplasmic fractions in wild-type (WT), CJD and FFI mice. Each RIP-Seq and control (input) library represents a pool of 12 to 16 co-immunoprecipitation samples out of 3 to 4 mice.
To control for post-homogenization artifacts, we conducted an experiment in which we prepared homogenates from WT and PrP-KO (Prnp-/-) mice of different genetic backgrounds (C57BL/6 and 129S4) and identified SNPs in RIP-Seq and control libraries to finally identify specifically co-purified mRNAs.
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| Contributor(s) |
Krost C, Kaczmarczyk L, Schleif M, Kolaitis R, Capece V, Taylor JP, Bonn S, Jackson WS |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
May 01, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Clemens Krost |
| E-mail(s) |
clemenskrost@gmx.de
|
| Phone |
+49-228-28752151
|
| Organization name |
German Center for Neurodegenerative Diseases (DZNE)
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| Lab |
AG Jackson
|
| Street address |
Sigmund-Freud-Str. 25
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| City |
Bonn |
| ZIP/Postal code |
53127 |
| Country |
Germany |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA246021 |
| SRA |
SRP041601 |
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